Chavany C, Le Doan T, Couvreur P, Puisieux F, Hélène C
Laboratoire de Biophysique, Muséum National d'Histoire Naturelle, INSERM U 201, CNRS URA 481, Paris, France.
Pharm Res. 1992 Apr;9(4):441-9. doi: 10.1023/a:1015871809313.
Adsorption of oligothymidylates on polyisobutyl- or polyisohexylcyanoacrylate nanoparticles was achieved in the presence of hydrophobic cations such as tetraphenylphosphonium chloride or quaternary ammonium salts. Results suggested that oligonucleotide adsorption on the nanoparticles was mediated by the formation of ion pairs between the negatively charged phosphate groups of the nucleic acid chain and the hydrophobic cations. The adsorption efficiency of oligonucleotide-cation complexes on nanoparticles was found to be highly dependent upon several parameters: oligonucleotide chain length, nature of the cyanoacrylic monomer, hydrophobicity of cations used as ion-pairing agents, and ionic concentration of the medium. Carrier capacity of polyisohexylcyanoacrylate nanoparticles for oligothymidylates (16 nucleotides) complexed with cetyltrimetylammonium bromide in the presence of 0.15 M NaCl was determined to be 5 mumol/g polymer. The in vitro protection of oligothymidylates adsorbed to nanoparticles against degradation by a 3'-exonuclease (snake venom phosphodiesterase) was also demonstrated. These results showed that nanoparticles can be considered as convenient carriers for the protection and delivery of oligonucleotides to cells in culture and for future applications in vivo.
在疏水性阳离子如四苯基氯化鏻或季铵盐存在的情况下，寡聚胸苷酸吸附到聚异丁基或聚异己基氰基丙烯酸酯纳米颗粒上。结果表明，核酸链带负电荷的磷酸基团与疏水性阳离子之间形成离子对介导了寡核苷酸在纳米颗粒上的吸附。发现寡核苷酸 - 阳离子复合物在纳米颗粒上的吸附效率高度依赖于几个参数：寡核苷酸链长度、氰基丙烯酸单体的性质、用作离子配对剂的阳离子的疏水性以及介质的离子浓度。在0.15 M NaCl存在下，聚异己基氰基丙烯酸酯纳米颗粒对与十六烷基三甲基溴化铵复合的寡聚胸苷酸（16个核苷酸）的载药量测定为5 μmol/g聚合物。还证明了吸附到纳米颗粒上的寡聚胸苷酸在体外对3'-外切核酸酶（蛇毒磷酸二酯酶）降解的保护作用。这些结果表明，纳米颗粒可被视为用于保护寡核苷酸并将其递送至培养细胞以及未来体内应用的便利载体。
